In the second decade of the 20th-century, a number of Virginia Mennonite Conference (Mennonite Church) leaders believed there should be a church school in the East. It was observed that a great many Mennonite young people who attended the local high schools were being lost to the church. It was to prevent this loss and to establish a school that would promote the cause of the Mennonite Church, that steps were taken to organize a church school in the East. It was difficult to find a permanent location for the school. Warwick County and Alexandria, Virginia, were considered as possible locations in 1914 and 1915, but these were rejected because they were off center from the total Mennonite population in the East. The Assembly Park, a 16-acre forest area, 1 1/2 miles northwest of Harrisonburg, with a large, three-story frame building which had been previously used as an industrial school, was chosen as the location, since it was located near the border between the Middle and the Northern districts of the Virginia Conference. This property was purchased in 1916, and used until the winter of 1920, when the college was moved to its permanent location on the hill west of the Assembly Park. The first building on the new site was a large (50 x 120 feet) three-story tile stucco building providing classrooms, dormitories, dining hall and kitchen, and administration offices. In 1926 a south annex was constructed providing additional dormitories on the third and fourth floors, a new chapel on the first floor, and a science laboratory and dining room in the basement. With the exception of the gymnasium, no further major building enterprise was undertaken for more than a decade. In 1938 Vesper Heights Observatory was constructed as a class project. Its development attracted wide attention.

In 1940 building operations were begun again on a large scale. The new north annex provided for science laboratories in the basement, a library on the entire first floor, and an infirmary on the second and third floors. The old frame building in the Assembly Park was razed and some of the material used in the construction of an industrial arts building. The largest unit of construction in the early 1940s was the auditorium with a seating capacity of 1,500. An assembly room in the basement provided accommodations for 500.

During World War II and several years following, building operations were practically at a standstill except for emergency building. In 1949 the board of trustees decided to undertake building again on a larger scale. Work was begun on the largest single building unit in the history of the school to that time—the women's dormitory, which accommodated 250 persons and included a larger kitchen and dining room as well as additional classrooms; it was completed in 1953.

The building programs have not been the most important phases of life at Eastern Mennonite College. Curriculums have been added and expanded; accreditment has been sought and attained. Work of college grade was offered first in 1920. In the following years, two and three years of college work were offered. In 1930 the College was accredited by the state as a standard junior college. Two years later the College received state approval for a two-year teacher's training course leading to a normal professional certificate. A Bible course of college grade has been offered from almost the first. The course has been expanded along with the general college work, so that in 1937, a four-year Bible course leading to the Th.B. degree was offered. A four-year liberal arts college program was initiated in 1945. The Virginia State Board of Education in 1947 gave Eastern Mennonite College the rating of a standard four-year college with permission to grant the A.B., B.S., B.S. in Education, B.R.E., and Th.B. (6-yr.) degrees.

The college in 1955 offered the following curricula: Bachelor of Arts, Bachelor of Science, Premedical Course, Bachelor of Science in Home Economics, Bachelor of Arts in Secondary Education, Bachelor of Science in Secondary Education, Bachelor of Science in Elementary Education, and Bachelor of Science in Nursing; in the Bible School, the Christian Workers' Course, Junior College Bible Course, Bachelor of Religious Education, and Bachelor of Theology.

In 1965 the graduate seminary had evolved as Eastern Mennonite Seminary. Other graduate programs were initiated in the 1990s. Because of the graduate programs, Eastern Mennonite College became Eastern Mennonite University in August 1994.

These increased offerings and accreditment by the State Board meant much from the standpoint of enrollment. In the 1930s the enrollment was around 50 students; by 1952 it had increased to 260, almost exclusively members of the Mennonite Church (MC). The College also operated a strong high-school division with about 200 students. In 1955-56 the total enrollment was 623, with 381 in the college, and 242 in the high school. In 2007 Eastern Mennonite University had over 1400 students.

By 1955-56 the College was staffed by 41 teaching faculty members. Six of this number had the doctor's degree, or its equivalent, and two were candidates.

A large variety of extracurricular activities was provided. The Christian service activities in the 1950s were under the direction of a Director of Christian Service and the Young People's Christian Association. This provided an outlet of expression for the religious emphasis in all departments of training. The college was characterized by a strong religious atmosphere and a conservative theological viewpoint. It aimed to train youth for service in the church and has for its motto "Thy Word Is Truth."

The school was owned and operated by the Virginia Mennonite Conference through a board of 17 trustees elected for a three-year term by the conference. In addition there was a Religious Welfare Committee of four elected by the conference.